The prime area of investigation of our total project is an assessment of the short and long term biological effectiveness of the vitamin D metabolite, 1,25(OH)2D3, and several closely related analogs, 1 alpha-OH-D3 in humans under normal and pathological conditions. In addition to ongoing clinical evaluation of long term (6-18 months) administration of 1,25(OH)2D3, other current studies include evaluation in animal models of the effects of pharmacological doses of tritiated 1,25(OH)2D3 both in terms of metabolism of the steroid as well as its biological effects in calcium and phosphorus homeostasis. Also we are studying in animal models the putative basis for "phosphate depletion" as being a physiological stimulus or signal which may stimulate the renal production of 1,25(OH)2D3 by the kidney.